Frequently lost in the policy discussions about human embryonic stem
cells research are concrete realities that will determine how quickly
such research will result in treatments and cures. Scientists are conducting
research. Federal and local legislators are writing laws to broadly support
the research. Non-profit health organizations and private companies are
funding some of the most cutting-edge approaches. Here we will offer a
selection of current research programs, new lawmaking, and happenings
away from government and academia that will contribute to useful understandings
of stem cells.

Discussion on a proposal before the United Nations to institute a worldwide ban on all forms of human cloning has been suspended until some time in 2004. The United States, together with several other countries, initiated the proposal, which would have included a ban on research cloning as well as reproductive cloning. But a number of other countries, including Great Britain, objected to the ban on research cloning and wanted to suspend all debate on cloning until 2005. Following intense diplomatic and parliamentary maneuvering, the parties finally agreed to take up the matter in 2004. More about the activity at the United Nations concerning human cloning and a record of the vote to suspend discussion may be found at http://www.un.org/law/cloning.

United States

In April 2004, more than 200 members of the U.S. House of Representatives sent President Bush a letter, asking him to increase the number of human embryonic stem cell lines that should be eligible for public funding. Two months later, a group of U.S. Senators backed up their colleagues in the House and sent a similar letter to the White House. In essence, the signers were trying to get the President to change his mind about stem cell lines used for research so that Congress does not have to create a legislative solution.

On 9 August 2001, President George W. Bush made a long-awaited announcement
regarding research on human embryonic stem cells. The President declared
that federal funds could be used to support research on cell lines that
were already in existence on that date. He also said that no federal dollars
could be used in research on new human embryonic cell lines. At the time,
many scientists were pleased that the research was not banned altogether.
Others were disappointed that the White House had effectively prohibited
the creation of new stem cell lines using federal funding.

Although some 70 different human embryonic stem cell lines are eligible
for use in federally funded research, it appears that in reality only
about nine or so are of immediate use to scientists. As researchers look
ahead to potential clinical trials with stem cells, it is becoming apparent
that few, if any, of these lines will have any therapeutic value, in part
because they were grown along with “feeder” cells from mice.
Many researchers would prefer to work on “all human” culture
systems, but the development of these systems has been blocked by the
White House’s regulations.

In large part as a result of the President’s decision, the U.S.
Congress has taken a renewed interest in legislation regulating embryo
research. Most recently, in February 2003, Senator Arlen Specter, Republican
of Pennsylvania, and others introduced legislation that would expand research
options by allowing cells to be newly isolated from embryos, including
cloned embryos—those created for research purposes only and not
through fertilization. The legislation would outlaw reproductive cloning.

Although embryonic stem cell research is not illegal in the United States, two states, California and New Jersey, have passed legislation permitting it and others are considering such laws.

California

Californians Approve $3 Billion for Stem Cells(November 2004)

On November 2, 2004, voters in California approved Proposition 71, which allows the state to borrow $3 billion for research on stem cells. The measure passed with 59 percent of the vote.

Californians to Vote on Funding Stem Cell Research(September 2004)

Voters in California will be the first in the country to cast ballots on an initiative that supports human stem cell research in a concrete way: by providing funding. The Stem Cell Research and Cures Initiative would authorize the sale of about $3 billion bonds over the course of ten years. The bulk of the money raised by the bonds would go to support a wide range of stem cell research.

The proposal would also create a new entity, the California Institute for Regenerative Medicine. This institute would distribute grants and loans to individual researchers and research programs, as well as develop regulatory standards and create new research facilities as needed. The initiative, Proposition 71, will appear on the ballot November 2nd, 2004.

California is at the forefront of a new push not only to allow but also to encourage stem cell research. A new law signed on 23 September 2002 by Governor Gray Davis specifically allows research on embryos, including the use of cloned embryos. The law prohibits reproductive cloning. The law does not appropriate funds specifically for research, but research centers may direct non-federal money to stem cell studies.

California is at the forefront of a new push not only to allow but
also to encourage stem cell research. A new law signed on 23 September
2002 by Governor Gray Davis specifically allows research on embryos,
including the use of cloned embryos. The law prohibits reproductive
cloning. The law does not appropriate funds specifically for research,
but research centers may direct non-federal money to stem cell studies.

In addition, California Health & Safety Codes (§ 123440, 24185,
24187, 24189, 12115-7) and Business & Professions Codes( §16004,
§16105) provide for the revocation of licenses issued to businesses
for violations relating to human cloning. The codes also prohibit the
purchase or sale of ovum, zygote, embryo, or fetus for the purpose of
cloning human beings. There are civil penalties for violations. (Source:
National Conference of State Legislatures.)

New Jersey

New Jersey is frequently on the cutting edge of science and public policy. It is now the second state (after California) to pass legislation allowing embryonic stem cell research.

A law signed on January 2, 2004, by Governor James E. McGreevey permits research and use of human embryonic stem cells, germ cells, and human adult stem cells from any source. It also requires physicians treating infertility patients to provide these patients with information about donating human embryos after infertility treatment.

Australia

Australia bans all human cloning whether for reproduction or research.
This includes a ban on embryo splitting and other techniques that might
create a clone without fertilization. But Australia does allow the use
of embryos remaining after assisted reproduction, as long as those embryos
were created before 5 April 2002. This federal law supersedes all previous
state-level laws concerning embryonic stem cell and cloning research.

The United Kingdom’s Human Fertilisation and Embryology Authority (HFEA) has issued a license that will allow researchers to create colonies of human stem cells for the purposes of research. The license specifies that the stem cells will be used for research purposes only and not to clone a human being.

The license was granted to the Newcastle Center for Life on August 11, 2004, and is good for one year. After that year, the researchers may continue to work on any stem cell lines (the isolated populations of stem cells) that they have established. They will not be able to continue the cloning and stem cell isolation procedures unless a new license is issued.

New lines will increase research opportunities, but not for most American researchers.

In March 2002, a research group from King's College in London received one of the first licenses from the United Kingdom 's Human Fertilisation and Embryology Authority to isolate stem cells from human embryos and establish cultures of stem cells that could be propagated or frozen. Those cell cultures, or lines, now exist and will be part of the UK's Stem Cell Bank. A description of the isolation of the cells was reported in the October 2003 issue of the journal Reproductive BioMedicine Online.

The group, led by Stephen Minger and Susan Pickering, created three separate stem cell populations from 58 embryos. The group used an approach that is valuable for research purposes but is unlikely to yield therapies immediately. They were able to use embryos that had been created through in vitro fertilization for reproductive purposes but that had ultimately not been selected because they carried gene mutations. The women undergoing fertility treatments donated the embryos.

Although the creation of the cell lines was not a surprise, the availability of these cells is significant. Researchers from other countries have anecdotally reported the establishment of stem cell lines, but this is the first scientific publication describing the isolation of stem cells under government guidelines specific to stem cell research.

More important, the deposit to the Stem Cell Bank is the bellwether of many more stem cell lines to come, both from the UK licenses and, presumably, from researchers in other countries operating under their respective regulations.

Thus, more materials will be accessible to more researchers, who can use them to design informative experiments, which is what the field needs in order to advance. Researchers in the United States will not be able to use Federal funding for work on these lines, as they were created after 9 August 2001 (see section on the United States).

Background

The United Kingdom
has since 1990 allowed research using embryos remaining after assisted
reproductive procedures. Laws in the UK also allow for the creation of
embryos for research. Most of this research falls under the control of
the Human Fertilisation and Embryology
Authority (HFEA). The 1990 law covers the use of such embryos for
research in reproductive biology, but a new interpretation of the law
in 2001 expanded this to include many types of basic research. The allowance
for cloning is being challenged by several groups.

The United Kingdom is developing a stem cell bank that would make a
variety of characterized and newly derived stem cell cultures available
to researchers. The Human Fertilisation and Embryology Authority would
oversee the selection of cell lines to be established and included in
the bank. The Medical Research Council would run the bank.

Switzerland

The Swiss Parliament is
considering the possibility of allowing research on stem cells derived
from stored embryos remaining at the end of assisted reproduction procedures
if they were frozen at seven or fewer days of development. The research
could only be for non-commercial, “therapeutic” purposes,
and the proposal bans the creation of embryos specifically for research
purposes. In addition, work may eventually be allowed on a limited number
of stem cell cultures imported from other countries.

This legislation is notable because the Swiss Constitution broadly
prohibits research using human embryos and even sets controls over
the number of eggs that may be fertilized and developed outside a woman’s
body during fertility treatments. This control has resulted in between
1,000 and 5,000 embryos being frozen in Switzerland (by comparison, there
may be about 400,000 in the United States). If the Swiss legislation passes,
the nation’s thousands of embryos may become available to researchers.
Thus, a country that has seemed averse to human embryo research may find
itself at the forefront of stem cell research.

RESEARCHERS

John Gearhart is Professor of Gynecology and Obstetrics at the
Johns Hopkins University School of Medicine in Baltimore, Maryland. He
was the first to describe the successful culturing of human embryonic
germ cells and published a landmark 1998 paper on human primordial germ
cells. Aware of the political ramifications of the research, his laboratory
used no federal money during the course of that study (though it would
have been eligible for funding). In addition to his work on various aspects
of human development, he has become involved in various bioethics projects.
He is a member of the Project in Cellular Engineering, Ethics, and Public
Policy at the Berman Institute of Bioethics at Johns Hopkins.

Ron McKay is Senior Investigator at the National Institute of
Neurological Disorders and Stroke, National Institutes of Health in Bethesda,
Maryland. McKay’s laboratory studies the process by which stem cells
become specific cell types, known as differentiation. His laboratory has
been designated to characterize the nine or so embryonic stem cell lines
that are currently available to federally funded researchers. This project,
which could take several years, involves completely describing the cell
lines, their growth characteristics, the conditions they require to grow
robustly, which genes are turned on or off, and so on. This information
is standard for all newly created cell lines and will help researchers
decide which lines may be best for their experiments. His laboratory is
also known for experiments that led to the alleviation of symptoms in
a mouse model of Parkinson's disease.

Douglas Melton is the Thomas Dudley Cabot Professor of the Natural Sciences at Harvard University and a co-director of the Harvard Stem Cell Institute. His research focuses generally on the development of the pancreas and more specifically on stem cells, particularly those that might be important in the treatment of diabetes. He was the principal investigator on the project that yielded 17 new stem cell lines, paid for completely with private funds. These cell lines are currently available to all investigators using private funds for their research. Melton has testified before the U.S. Senate on stem cell research concerns, and he is active in a variety of groups concerned with the conduct of stem cell research, including the Juvenile Diabetes Foundation International.

James Thomson is Professor of Anatomy at the University of Wisconsin
Medical School in Madison. He was the first to describe the in vitro
culture of human embryonic stem cells. He currently studies the factors
that promote cell self-renewal, the maintenance of pluripotency, and the
pathways leading to the differentiation to specific cell types. His laboratory
recently demonstrated a novel use of a specific gene-targeting technique
for human embryonic stem cells. The technique, called homologous recombination,
allows scientists to remove or insert a specific stretch of DNA—sometimes
even a whole gene—from a single cell. The study marked the first
time the procedure worked successfully in human stem cells, though it
is routinely used in mice. The potential applications for this technology
include research on gene therapy treatments.

Catherine Verfaillie is Director of the Stem Cell Institute at
the University of Minnesota in Minneapolis. Her research focuses on how
the identities of various tissues are determined. That is, how does muscle
become muscle and not skin, or bone? In the process of this research,
her team isolated multipotent adult progenitor cells—human cells
that apparently do not yet have even a general identity determined. Although
they might not be stem cells in the strictest sense, they appear to give
rise to a variety of cell types found in virtually all organs. These included
the tissue that gives rise to the nervous system, to the musculoskeletal
system, and to skin.

Irving Weissman is the Karel and Avice Beekhuis Professor of Cancer
Biology, Professor of Pathology and developmental biology at Stanford
University’s School of Medicine in California. He was recently appointed
to direct the newly formed Stanford Institute for Cancer/Stem Cell Biology
and Medicine. One of the earliest to recognize the breadth and depth of
potential stem cell therapies, Weissman founded two companies (SyStemix
and StemCells, Inc.) and has been an outspoken proponent of cloning for
research purposes. He heads the US National Academy of Science’s
panel on cloning, and as such is frequently a lightning rod for opponents
of stem cell research. He is a pioneer of the field called “adult
stem cell biology” and has isolated of various blood cell precursors
in mice.